crossing96/oncoscreening huggingface dataset:
Exercise in primary care after robot-assisted radical cystectomy for urinary bladder cancer - effects on postoperative complications: a secondary analysis of a randomised controlled trial.	OBJECTIVE: An exercise programme in primary care soon after radical cystectomy for urinary bladder cancer was previously evaluated regarding its effects on physical function. A secondary aim, presented herein, was to evaluate the programme in terms of its effect on postoperative complications. MATERIALS AND METHODS: Patients who were planned for robot-assisted radical cystectomy for urinary bladder cancer at Karolinska University Hospital between September 2019 and October 2022 were invited to participate. At discharge from hospital, they were randomised to intervention group including aerobic and resistance exercises with physiotherapist in primary care twice a week for 12 weeks and daily walks, or to unsupervised home-based exercise including daily walks. Readmission rates between 30 and 90 days after discharge, and complications according to Clavien Dindo were collected from the medical records and analysed. RESULTS: Ninety patients were randomised, with a mean (SD) age of 72 (9) years. Readmission rates between 30 and 90 days showed no difference between the groups. For readmitted patients, the intervention group had significantly fewer complications reported as Clavien Dindo grade 2 compared to the control group.  Conclusion: An exercise programme in primary care soon after robot-assisted radical cystectomy appears to be safe for patients, as measured by hospital readmission rates.  Trial registration: Clinical Trials (NCT03998579).	bladder
A new perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy.	INTRODUCTION: Bladder cancer was recognized as one of the most common malignant tumors in the urinary system, and treatment options remained largely limited to conventional surgery, radiotherapy, and chemotherapy, which limited patient benefits. METHODS: Researchers constructed an RNA transcriptome map of bladder cancer by integrating single-cell RNA sequencing and clinical data, identifying potential molecular targets for diagnosis and treatment. We also verified the antitumor activity of the target through in vitro experiment. RESULTS: A distinct tumor cell subpopulation characterized by elevated S100A8 expression exhibited high copy number variation, high stemness, and low differentiation. It interacted with myeloid cells via the MIF-(CD74+CD44) and MIF-(CD74+CXCR4) signaling pathways. This study underscored KDELR2's role in promoting cell proliferation, invasion, and migration, providing new therapeutic insights. Prognostic analysis revealed that KDELR2 correlated with poor survival, higher immune scores, and increased macrophage infiltration. DISCUSSION: The findings suggested that patients with high KDELR2 expression might benefit from immune checkpoint therapy. KDELR2 was also shown to enhance bladder cancer cell proliferation, invasion, and migration, highlighting it as a promising target for macrophage-focused drug development.	bladder
HSPE1 Inhibits Bladder Cancer Ferroptosis via a Glutathione-Dependent Mechanism by Suppressing GPX4.	Bladder cancer (BLCA) remains a significant health risk despite advancements in medical science that have led to reduced incidence and death rates. While the molecular regulatory mechanisms of BLCA are not yet fully understood, HSPE1, a member of the heat shock protein family, is regarded as a reliable prognostic target for BLCA. Using data from The Cancer Genome Atlas (TCGA) database, the differential expression levels of HSPE1 and its relationship to GPX4 were examined. Gene Set Enrichment Analysis was used to carry out HSPE1 pathway enrichment analysis. HSPE1 and GPX4 expressions in cells were assessed using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting. Cell cycle alternations and apoptosis were evaluated using flow cytometry. Cell proliferation was assessed using EdU and colony formation assays. The lactate dehydrogenase (LDH) test, glutathione (GSH) measurement, and Liperfluo assay were utilized to evaluate the presence of ferroptosis in cells. BLCA tissues and cells had significantly elevated levels of HSPE1. In BLCA, high expression of HSPE1 inhibited apoptosis while promoting cell proliferation and cell cycle progression. Significant enrichment of HSPE1 was found in the GSH metabolism and ferroptosis pathways, according to pathway enrichment analysis. In cancer cells, HSPE1 promoted GSH accumulation, decreased lipid peroxidation, and inhibited cell ferroptosis, as demonstrated in a rescue experiment with the ferroptosis inhibitor Fer-1. Pearson correlation analysis unveiled a substantial positive correlation between HSPE1 and the ferroptosis regulator GPX4. According to the results of rescue experiments, HSPE1 regulated GPX4 to affect cell lipid peroxidation levels and GSH accumulation. HSPE1 plays a crucial role in regulating GPX4 to prevent BLCA cells from undergoing ferroptosis, with this control mechanism dependent on GSH.	bladder
Prognostic model based on disulfidptosis-related lncRNAs for predicting survival and therapeutic response in bladder cancer.	BACKGROUND: With poor treatment outcomes and prognosis, bladder cancer remains a focus for clinical research in the precision oncology era. However, the potential of disulfidptosis, a novel cell death mechanism, and its related long non-coding RNAs to support selective cancer cell killing in this disease is still unclear. METHODS: We identified key disulfidptosis-related lncRNAs in bladder cancer, constructed a prognostic risk model with potential therapeutic targets, and confirmed the findings through quantitative PCR analysis. RESULTS: We identified five crucial lncRNAs (AC005840.4, AC010331.1, AL021707.6, MIR4435-2HG and ARHGAP5-AS1) and integrated them into a predictive model centered on disulfidptosis-associated lncRNAs. Reliability and validity tests demonstrated that the lncRNA prediction index associated with disulfidptosis effectively discerns patients' prognosis outcomes. Additionally, high-risk patients exhibited elevated expression levels of genes involved in the PI3K-Akt signaling pathway, extracellular matrix organization, and immune escape mechanisms, which are associated with poor prognosis. Notably, high-risk patients demonstrated higher sensitivity to Sorafenib, Oxaliplatin and MK-2206, underscoring the promise of these lncRNAs as precise therapeutic targets in bladder cancer. CONCLUSION: By revealing the predictive importance of disulfidptosis-associated lncRNAs in bladder cancer, our research offers new perspectives and pinpoints potential therapeutic targets in clinical environments.	bladder
PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder.	PURPOSE: Placental alkaline phosphatase (PLAP) is a protein with a poorly understood function that is normally only expressed in the placenta. In cancer, PLAP expression is a hallmark of germ cell neoplasms, but it can also occur in urothelial carcinoma. To evaluate the potential clinical significance of PLAP expression in bladder cancer, METHODS: PLAP protein was analyzed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format. RESULTS: PLAP staining was absent in normal urothelial cells but was observed in 15.9% of urothelial carcinomas, including 282 (11.5%) with weak, 57 (2.3%) with moderate, and 51 (2.1%) with strong staining. PLAP positivity occurred in 4.1% of 413 pTa G2 low-grade, 10.2% of 176 pTa G2 high-grade, and 7.2% of 97 pTa G3 tumors (p = 0.0636). As compared to pTa tumors, the PLAP positivity rate was markedly higher in 1341 pT2-4 carcinomas (19.8%, p < 0.0001). Within pT2-4 carcinomas, PLAP staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence-free survival, and cancer-specific survival (p > 0.25). However, PLAP positivity was linked to p16 positivity (p = 0.0185), GATA3 positivity (p < 0.0001), and p63 expression loss (p = 0.0456). CONCLUSION: In summary, these data show that PLAP is expressed in a significant fraction of pT2-4 urothelial carcinomas, unrelated to cancer aggressiveness but associated with specific molecular features. Once anti-PLAP cancer drugs become effective, urothelial carcinoma is a candidate tumor entity for clinical evaluation.	bladder
Clinical efficacy and safety of organ-sparing cystectomy: a systematic review and meta-analysis.	BACKGROUND: The clinical safety and efficacy of organ-sparing cystectomy (OSC) are subjects of ongoing debate, particularly concerning the potential increased risk of recurrence when retaining additional organs and its effectiveness in preserving sexual and urinary functions. METHODS: Adhering to the PRISMA 2020 statement and AMSTAR Guidelines, we conducted a systematic literature search up to February 2024 using PubMed, Embase, and Web of Science. The comparison focused on the clinical safety and effectiveness of OSC and standard radical cystectomy (SRC) in the treatment of bladder tumors. Our assessment covered several dimensions: Surgical safety outcomes (operation time, length of stay (LOS), estimated blood loss (EBL), and complications), oncological safety outcomes (recurrence rate, positive surgical margin rate, overall survival, and cancer-specific survival), and functional efficacy outcomes (daytime and nighttime urinary incontinence at 6 and 12 months, clean intermittent catheterization (CIC) rate, and erectile function within and after 1 year). RESULTS: The analysis included 19 eligible studies, encompassing 2,057 patients (1,189 OSC patients and 768 SRC patients). OSC demonstrated significant benefits in terms of erectile function and urinary continence without impacting CIC rates. No significant differences were observed in recurrence rate, positive surgical margin rate, overall survival, and cancer-specific survival. Furthermore, OSC and SRC were comparable in surgical safety outcomes, including operating time, LOS, EBL, and complications. CONCLUSIONS: OSC offers notable advantages in erectile function and urinary continence. Despite limited clinical practice and potential selection bias, urologists may still consider OSC more based on their experience and specific patient factors.	bladder
Methionine-driven YTHDF1 expression facilitates bladder cancer progression by attenuating RIG-I-modulated immune responses and enhancing the eIF5B-PD-L1 axis.	The impact of amino acids on tumor immunotherapy is gradually being uncovered. In this study, we screened various essential and non-essential amino acids and found that methionine enhances mRNA methylation and reduced the activation of Type I interferon pathway in bladder cancer. Through RNA sequencing, point mutations, MB49 mouse tumor models, and single-cell RNA sequencing, we demonstrated that high methionine levels elevate the expression of m(6)A reader YTHDF1, promoting the degradation of RIG-I, thereby inhibiting the RIG-I/MAVS-mediated IFN-I pathway and reducing the efficacy of tumor immunotherapy. Additionally, immunoprecipitation and mass spectrometry revealed that YTHDF1 binds to the eukaryotic translation initiation factor eIF5B, which acts on PD-L1 mRNA to enhance its translation and promote immune evasion. By intravesical administration of oncolytic bacteria VNP20009, we effectively depleted methionine locally, significantly prolonging mouse survival and enhancing immune cell infiltration and differentiation within tumors. Multiplex immunofluorescence assays in bladder cancer immunotherapy patients confirmed our findings. Our research elucidates two mechanisms by which methionine inhibits bladder cancer immunotherapy and proposes a targeted methionine depletion strategy that advances research while minimizing nutritional impact on patients.	bladder
Real-world Evidence for Enfortumab Vedotin in Patients with Metastatic Urothelial Cancer: An Austrian Multicentre Study.	AIM: Enfortumab vedotin (EV) represents a novel treatment for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) refractory to platinum-based chemotherapy and PD(L)-1 containing therapies. Real-world data are crucial for informing health policy decisions and validating clinical trial findings. METHODS: We conducted a multicentre, retrospective real-world analysis comprising 128 patients with la/mUC from 16 Austrian centres treated with EV from April 2022 to April 2024, presenting the second largest real-world cohort to date. Data were analysed for efficacy and safety parameters. RESULTS: The median age was 69 years, the objective response rate 31% and the disease control rate 47%, with 9% of patients exhibiting a complete remission, 23% a partial remission and 16% a stable disease. After a median follow-up of 6.2 months, the median progression-free survival (mPFS) and the median overall survival (mOS) reached 4.8 and 10.75 months, respectively. Patients with good ECOG PS 0-1, metachronous metastatic disease and absence of liver metastases had significantly better OS. No difference in efficacy was observed in patients who received a reduced dose EV after experiencing adverse events. The safety profile was acceptable, showing grade ≥3 TRAEs in 25.8% of patients. CONCLUSION: In our real-world population, the administration of EV was feasible and effective, with no new safety signals. Lower efficacy data compared to previous trials might be explained by the use in later therapy lines and in patients with poorer ECOG PS. Our data corroborate the efficacy and safety of EV monotherapy in later lines.	bladder
Impact of smoking exposure on disease progression in high risk and very high-risk nonmuscle invasive bladder cancer patients undergoing BCG therapy.	INTRODUCTION: The nonmuscle invasive bladder cancer treated with BCG instillations in patients who smoke could potentially lead to poorer oncological results in the light of the new EAU risk groups classification for NMIBC that did not include BCG treated patients or smoking status. PATIENT AND METHODS: Outcomes from 1313 patients with nonmuscle invasive bladder cancer treated with TURBT, re-TURBT and BCG instillations at 13 academic hospital centers, since 2002, has been included in this retrospective study. The study variables, including cumulative smoking exposure have been analyzed. A multivariable Cox proportional hazard model was used to assess associations between smoking variables and disease progression and repeated in the EAU high risk and very high-risk group. The statistical significance threshold was set at 0.05, and the statistical analysis was performed using Stata/SE version 17 (StataCorp, College Station, TX, USA). RESULTS: Cox regression analysis revealed in 1313 patients diagnosed with T1G3 NMIBC that patients with a history of heavy and long-term smoking faced a more than twofold increased risk of disease progression compared to nonsmoker patients (HR 2.35; 95% CI: 1.7-3.2; P < 0.01) and a significantly poorer PFS for patients with a history of heavy long-term smoke exposure (P < 0.01). Patients with heavy long-term smoking exposure according to the EAU21 high-risk group had a PFS comparable to very high-risk patients and high-risk patients with heavy long-term smoking exposure showed a higher risk of progression when compared to the high-risk group (HR 1.4; 95% CI: 1.3-1.6; P < 0.01). CONCLUSIONS: This study adds valuable information on the relationship between smoking and the progression of NMIBC and BCG therapy. The findings emphasize the need for healthcare providers to consider a patient's smoking history when managing NMIBC and express the need for individualized smoking cessation counseling and individualized treatment approach.	bladder
Survival After Radical Cystectomy for Bladder Cancer: Development of a Fair Machine Learning Model.	"BACKGROUND: Prediction models based on machine learning (ML) methods are being increasingly developed and adopted in health care. However, these models may be prone to bias and considered unfair if they demonstrate variable performance in population subgroups. An unfair model is of particular concern in bladder cancer, where disparities have been identified in sex and racial subgroups. OBJECTIVE: This study aims (1) to develop a ML model to predict survival after radical cystectomy for bladder cancer and evaluate for potential model bias in sex and racial subgroups; and (2) to compare algorithm unfairness mitigation techniques to improve model fairness. METHODS: We trained and compared various ML classification algorithms to predict 5-year survival after radical cystectomy using the National Cancer Database. The primary model performance metric was the F(1)-score. The primary metric for model fairness was the equalized odds ratio (eOR). We compared 3 algorithm unfairness mitigation techniques to improve eOR. RESULTS: We identified 16,481 patients; 23.1% (n=3800) were female, and 91.5% (n=15,080) were ""White,"" 5% (n=832) were ""Black,"" 2.3% (n=373) were ""Hispanic,"" and 1.2% (n=196) were ""Asian."" The 5-year mortality rate was 75% (n=12,290). The best naive model was extreme gradient boosting (XGBoost), which had an F(1)-score of 0.860 and eOR of 0.619. All unfairness mitigation techniques increased the eOR, with correlation remover showing the highest increase and resulting in a final eOR of 0.750. This mitigated model had F(1)-scores of 0.86, 0.904, and 0.824 in the full, Black male, and Asian female test sets, respectively. CONCLUSIONS: The ML model predicting survival after radical cystectomy exhibited bias across sex and racial subgroups. By using algorithm unfairness mitigation techniques, we improved algorithmic fairness as measured by the eOR. Our study highlights the role of not only evaluating for model bias but also actively mitigating such disparities to ensure equitable health care delivery. We also deployed the first web-based fair ML model for predicting survival after radical cystectomy."	bladder
CD105-microvessel density analysis and its clinical value in urothelial carcinoma of bladder patients.	BACKGROUND: Endoglin/CD105-microvessel density (CD105-MVD) is identified as one of the most potential methods for semi-quantification of angiogenesis in human cancer tissues. Present study aimed to examine the diagnosticand prognostic value of CD105-MVD in two clinically distinct subtypes of urothelial carcinoma of bladder (UCB) namely non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) patients. METHODS: Message expression of endoglin was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and MVD measurement was done by immunohistochemical staining in 90 UCB [NMIBC: 60; MIBC: 30] patients. SEM studies were carried out to examine tumor vasculature and extent of neoangiogenesis in NMIBC and MIBC patients. RESULTS: Elevated message expression of CD105 showed statistical significance with tumor stage, grade, smoking/tobacco chewing history in NMIBC andage in MIBC cohort. Higher values of CD105-MVD showed statistical relevance with tumor stage, grade, size, smoking/tobacco chewing history in NMIBC cohort. Kaplan Meier test identified high CD105-MVD as strong predictor of poor RFS in NMIBC patients. CONCLUSIONS: Association of CD105 expression and MVD with the clinicohistopathological features as well as poor survival outcomes potentially identify it as a preferred marker of clinical significance in a given cohort of UCB patients.Clinical significanceStrong association of CD105 at message level with the demographics of UCB patients identifies it as a marker of diagnosis in a given cohort of patients.Survival analysis examined CD105-MVD as an independent strong predictor of poor recurrence free survival in NMIBC patients.Present study provides clear evidence of increased vascular density, vascular sprouts proliferation and new blood vessel formation with disease aggressiveness indicating CD105 as a preferred marker of neoangiogenesis in the given cohort of patients.The study describes CD105-MVD as a biomarker of diagnosis and prognosis with the sensitivity of 91.67% and 93.33% in a given cohort of NMIBC and MIBC patients.	bladder
Identification of anoikis-related molecular patterns and the novel risk model to predict prognosis, tumor microenvironment infiltration and immunotherapy response in bladder cancer.	BACKGROUND: Anoikis, a unique form of cell death, serves as a vital part of the organism's defense by preventing shedding cells from re-attaching to the incorrect positions, and plays pivotal role in cancer metastasis. Nonetheless, the specific mechanisms among anoikis, the clinical prognosis and tumor microenvironment (TME) of bladder cancer (BLCA) are insufficiently understood. METHOD: BLCA patients were classified into different anoikis subtypes based on the expression of candidate anoikis-related genes (ARGs), and differences in the clinicopathological features, TME, immune cell infiltration, and immune checkpoints between two anoikis subtypes were analyzed. Next, patients in the TCGA cohort were randomized into the train and test groups in a 1:1 ratio. Subsequently, the anoikis-related model was constructed to predict the prognosis via utilizing the univariate Cox, LASSO and multivariate Cox analyses, and validated internally and externally. Moreover, the relationships between the risk score and clinicopathologic features, immune cell infiltration, immunotherapy response, and antitumor drug sensitivity were also analyzed. In addition, representative genes were evaluated using immunohistochemistry in clinical specimens, and in BLCA cell lines, functional experiments were performed to determine the biological behavior of hub gene PLOD1. RESULT: Two definite anoikis subgroups were identified. Compared to ARGcluster A, patients assigned to ARGcluster B were characterized by an immunosuppressive microenvironment and worse prognosis. Then, the anoikis-related model, including PLOD1, EHBP1, and CSPG4, was constructed, and BLCA patients in the low-risk group were characterized by a better prognosis. Next, the accurate nomogram was built to improve the clinical applicability by combining the age, tumor stage and risk Score. Moreover, immune infiltration and clinical features differed significantly between high- and low-risk groups. We also found that the low-risk group exhibited a lower tumor immune dysfunction and exclusion score, a higher immunophenoscore (IPS), had more sensitivity to immunotherapy. Eventually, the expression levels of three genes were verified by our experiment, and knockdown of PLOD1 could inhibit invasion and migration abilities in BLCA cell lines. CONCLUSION: These results demonstrated a new direction in precision therapy for BLCA, and indicated that the ARGs might be helpful to in predicting prognosis and as therapeutic targets in BLCA.	bladder
Orosomucoid 1 interacts with S100A12 and activates ERK signalling to expedite the advancement of bladder cancer.	The research endeavors to expound the role of ORM1 in bladder cancer (BCa) and the implied response mechanism. RT-qPCR and Western blotting examined ORM1 and S100A12 expression. Functional experiments assessed the cellular phenotypes. HDOCK and Co-IP confirmed the interaction of ORM1 and S100A12. Western blotting tested apoptosis- and ERK signaling-associated proteins. ORM1 and S100A12 were abundant in the BCa cells. ORM1 or S100A12 loss impaired cell proliferation, migration, and invasion, and aggravated cell apoptosis. ORM1 interacted with S100A12. ORM1 knockdown down-regulated S100A12 expression and inactivated ERK signaling.S100A12 overexpression or ERK activator reversed the impacts of ORM1 interference on ERK signaling and BCa cells. ORM1 mightdrive BCa via binding to S100A12 and activating ERK signaling.	bladder